1IHK

CRYSTAL STRUCTURE OF FIBROBLAST GROWTH FACTOR 9 (FGF9)

Summary for 1IHK

• Entry DOI: 10.2210/pdb1ihk/pdb
• Descriptor: GLIA-ACTIVATING FACTOR, PHOSPHATE ION (3 entities in total)
• Functional Keywords: b-trefoil fold, hormone-growth factor complex, hormone/growth factor
• Biological source: Homo sapiens (human)
• Cellular location: Secreted: P31371
• Total number of polymer chains: 1
• Total formula weight: 20181.48

Authors

Plotnikov, A.N.,Eliseenkova, A.V.,Ibrahimi, O.A.,Lemmon, M.A.,Mohammadi, M. (deposition date: 2001-04-19, release date: 2001-05-02, Last modification date: 2024-02-07)

Primary citation

Plotnikov, A.N.,Eliseenkova, A.V.,Ibrahimi, O.A.,Shriver, Z.,Sasisekharan, R.,Lemmon, M.A.,Mohammadi, M.
Crystal structure of fibroblast growth factor 9 reveals regions implicated in dimerization and autoinhibition.
J.Biol.Chem., 276:4322-4329, 2001

PubMed Abstract: Fibroblast growth factors (FGFs) constitute a large family of heparin-binding growth factors with diverse biological activities. FGF9 was originally described as glia-activating factor and is expressed in the nervous system as a potent mitogen for glia cells. Unlike most FGFs, FGF9 forms dimers in solution with a K(d) of 680 nm. To elucidate the molecular mechanism of FGF9 dimerization, the crystal structure of FGF9 was determined at 2.2 A resolution. FGF9 adopts a beta-trefoil fold similar to other FGFs. However, unlike other FGFs, the N- and C-terminal regions outside the beta-trefoil core in FGF9 are ordered and involved in the formation of a 2-fold crystallographic dimer. A significant surface area (>2000 A(2)) is buried in the dimer interface that occludes a major receptor binding site of FGF9. Thus, we propose an autoinhibitory mechanism for FGF9 that is dependent on sequences outside of the beta-trefoil core. Moreover, a model is presented providing a molecular basis for the preferential affinity of FGF9 toward FGFR3.

PubMed: 11060292
DOI: 10.1074/jbc.M006502200

Experimental method

X-RAY DIFFRACTION (2.2 Å)